Premium
Changes in the cytosolic Ca 2+ concentration and Ca 2+ ‐sensitivity of the contractile apparatus during angiotensin II‐induced desensitization in the rabbit femoral artery
Author(s) -
UshioFukai Masuko,
Yamamoto Hiromichi,
Toyofuku Kazuki,
Nishimura Junji,
Hirano Katsuya,
Kanaide Hideo
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703092
Subject(s) - angiotensin ii , contraction (grammar) , medicine , endocrinology , chemistry , extracellular , femoral artery , muscle contraction , cytosol , depolarization , renin–angiotensin system , vascular smooth muscle , calcium , stimulation , biophysics , biology , smooth muscle , biochemistry , receptor , blood pressure , enzyme
To investigate the underlying mechanism for the angiotensin II‐induced desensitization of the contractile response during the prolonged stimulation of the vascular smooth muscle, we determined the effects of angiotensin‐II on (1) cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and tension using fura‐2‐loaded medial strips of the rabbit femoral artery, (2) 45 Ca 2+ influx in ring preparations, and (3) Ca 2+ ‐sensitivity of the contractile apparatus in α‐toxin permeabilized preparations. In the presence of extracellular Ca 2+ , high concentrations of angiotensin‐II elicited biphasic increases in [Ca 2+ ] i and tension, which consisted of initial transient and subsequent lower and sustained phases. The 45 Ca 2+ influx initially increased after the application of 10 −6 M angiotensin‐II, and thereafter gradually decreased. At 20 min after the application, there was a discrepancy between the level of [Ca 2+ ] i and the extent of 45 Ca 2+ influx. The relationships between [Ca 2+ ] i and tension suggested that the angiotensin‐II‐induced increase in the Ca 2+ ‐sensitivity of the contractile apparatus was maintained during the desensitization of smooth muscle contraction. When 10 −6 M angiotensin‐II was applied during the sustained phase of contraction induced by 118 mm K + ‐depolarization, at 10 min after the application, the [Ca 2+ ] i levels were significantly lower and the tension levels were significantly higher than those prior to the application of angiotensin‐II. In conclusion, the decrease in [Ca 2+ ] i , which is partially due to the inhibition of the Ca 2+ influx, is mainly responsible for the desensitization evoked by high concentrations of angiotensin‐II, and angiotensin‐II seems to activate additional mechanisms which inhibit Ca 2+ signaling during prolonged stimulation.British Journal of Pharmacology (2000) 129 , 425–436; doi: 10.1038/sj.bjp.0703092